Enzyme Activity: Control


Enzymes are the metabolic catalysts that affect a multitude of physiological processes and responses. Tight control of enzyme activity is therefore essential in maintaining the steady state of all organisms.

Keywords: feedback inhibition; phosphorylation; allosteric regulation; covalent modification; proenzymes

Figure 1.

Feedback (end‐product) inhibition. As concentration of product E builds up, it acts to inhibit/regulate the catalytic activity of enzyme ‘a’.

Figure 2.

The kinetic profile for the allosteric protein ATCase. Shown is the sigmoid reaction velocity versus substrate concentration plots for ATCase when no effector is bound (solid line), when the positive effector ATP is bound at the allosteric site (dotted line) and when the negative effector CTP is bound to the allosteric site (dashed line). ATP serves as a positive effector to shift the curve to the left, meaning that lower substrate concentrations of aspartate and carbamoyl phosphate are required to achieve the same reaction velocity. CTP is a negative effector in this reaction, showing that higher substrate concentrations are required to achieve the same reaction velocities observed when ATP, or no effector, is bound.

Figure 3.

Transcriptional regulation of enzyme activity. Level of mRNA coding for a specific protein increases or decreases to match the cell's need for the macromolecule. RNAP‐RNA polymerase.

Figure 4.

Posttranslational regulation of enzyme activity. Nature has developed a complex system of regulatory mechanisms for controlling enzyme activity. In addition to regulating the synthesis of proteins (controlling transcription of mRNA and translation of proteins), a variety of covalent, posttranslational modifications have been created (ubiquitylation, phosphorylation, methylation, adenylation, etc.). Some of these modifications are reversible and can modulate protein degradation (ubiquitylation) or intrinsic activity (phosphorylation). Ub, ubiquitin.

Figure 5.

(a) The reversible phosphorylation of an enzyme, leading to enzymatic activation or inhibition. Specific serine, threonine and tyrosine residues in an enzyme (E) covalently accept a phosphoryl group from donor ATP. A group of enzymes known as kinases mediate phosphorylation. This mechanism of regulation is reversible. (b) Cleavage of the amino acid phosphoryl group is performed by a group of proteins known as phosphatases.

Figure 6.

Upon proteolytic cleavage, the zymogen (Z) undergoes a conformational change resulting in an active enzyme (E) with its active site exposed. Substrate (S) can now access the catalytic core. Irreversible proteolytic inhibition may also occur owing to the binding of specific protease inhibitors (I).


Further Reading

Cohen P (1982) The role of protein phosphorylation in neural and hormonal control of cellular activity. Nature 296: 613–620.

Hoeller D, Hecker CM and Dikic D (2006) Ubiquitin and ubiquitin‐like proteins in cancer pathogenesis. Nature Reviews. Cancer 6: 776–788.

Kantrowitz ER and Lipscomb WN (1990) E. coli aspartate transcarbamoylase: the molecular basis for a concerted allosteric transition. Trends in Biochemical Sciences 15: 53–59.

Kaul S, Kanthasamy A, Kitazawa M, Anantharam V and Kanthasamy AG (2003) Caspase‐3 dependent proteolytic activation of protein kinase C delta mediates and regulates 1‐methyl‐4‐phenylpyridinium (MPP+)‐induced apoptotic cell death in dopaminergic cells: relevance to oxidative stress in dopaminergic degeneration. European Journal of Neuroscience 18: 1387–1401.

Kumer SC and Vrana KE (1996) The intricate regulation of tyrosine hydroxylase activity and gene expression. Journal of Neurochemistry 67: 443–462.

Mathews CK, van Holde KE and Ahern KG (2000) Biochemistry, 3rd edn, chap. 10. Redwood City, CA: Benjamin/Cummings.

Pearson RB and Kemp BE (1991) Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations. Methods in Enzymology 200: 62–81.

Shintani T and Klionsky DJ (2004) Autophagy in health and disease: a double‐edged sword. Science 306: 990–995.

Sluis‐Cremer N, Temiz NA and Bahar I (2004) Conformational changes in HIV‐1 reverse transcriptase induced by nonnucleoside reverse transcriptase inbibitor binding. Current HIV Research 2: 323–332.

Stryer L (1995) Biochemistry, 4th edn, chap. 10. New York: WH Freeman.

Welchman RL, Gordon C and Mayer RJ (2005) Ubiquitin and ubiquitin‐like proteins as multifunctional signals, Nature Reviews. Molecular Cell Biology 6: 559–609.

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Nadaraia, Shorena, Yohrling, George J, Jiang, George C‐T, Flanagan, John M, and Vrana, Kent E(Jul 2007) Enzyme Activity: Control. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000861.pub2]